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. 2011 Apr 21:12:16.
doi: 10.1186/1471-2091-12-16.

The inhibition of the mammalian DNA methyltransferase 3a (Dnmt3a) by dietary black tea and coffee polyphenols

Arumugam Rajavelu  1 , Zumrad Tulyasheva, Rakesh Jaiswal, Albert Jeltsch, Nikolai Kuhnert
Affiliations

The inhibition of the mammalian DNA methyltransferase 3a (Dnmt3a) by dietary black tea and coffee polyphenols

Arumugam Rajavelu et al. BMC Biochem. .

Abstract

Background: Black tea is, second only to water, the most consumed beverage globally. Previously, the inhibition of DNA methyltransferase 1 was shown by dietary polyphenols and epi-gallocatechin gallate (EGCG), the main polyphenolic constituent of green tea, and 5-caffeoyl quinic acid, the main phenolic constituent of the green coffee bean.

Results: We studied the inhibition of DNA methyltransferase 3a by a series of dietary polyphenols from black tea such as theaflavins and thearubigins and chlorogenic acid derivatives from coffee. For theaflavin 3,3 digallate and thearubigins IC50 values in the lower micro molar range were observed, which when compared to pharmacokinetic data available, suggest an effect of physiological relevance.

Conclusions: Since Dnnmt3a has been associated with development, cancer and brain function, these data suggest a biochemical mechanism for the beneficial health effect of black tea and coffee and a possible molecular mechanism for the improvement of brain performance and mental health by dietary polyphenols.

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Figures

Figure 1
Figure 1
Purification of Dnmt3a catalytic domain. Fig. 1 Purified Dnmt3a-C separated on 12% SDS-PAGE gel and stained with colloidal Coomassie Blue. (M, Size marker for 116, 66.2, 45, 35 and 25 kDa; L, crude lysate; F, Flow through; W1, Wash1; W2, Wash2; E, Elution). The purified Dnmt3a-C protein runs at an apparent size of 36 kDa (highlighted with an arrow).
Figure 2
Figure 2
Structures of the compounds tested for Dnmt3a-C inhibition.
Figure 3
Figure 3
Methyltransferase activity of the purified Dnmt3a-C. Example of the methylation kinetics carried out with purified Dnmt3a-C. Initial slopes were determined by linear regression analysis of the initial linear parts of the reaction progress curves.
Figure 4
Figure 4
Initial screening of the 24 compounds for inhibition of Dnmt3a-C. Dnmt3a-C activity was determined in the presence of 100 μM compound. The control reaction was performed after adding a corresponding volume of DMSO.
Figure 5
Figure 5
Measurement of IC50 values for compounds N6, N7, N8 and N12. For compounds N6, N7, N8 and N11 DNA methylation kinetics were carried out at different concentration of the compounds to determine the IC50 value. The error bars show the maximal deviations in repeated experiments. IC50 values are valid by ±30%.
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